Tinnitus pitch does not always fall within the frequency range of hearing loss - a cross-sectional study on the mechanism of tinnitus production.

BACKGROUND: Clinically, we find that tinnitus patients often have hearing loss. According to the most accepted mechanism of tinnitus, that is, the spontaneous discharge and abnormal synchronization of neurons after afferent reduction, tinnitus frequency is closely related to the frequency of hearing loss. OBJECTIVE: The purpose of this study was to investigate the correlation of tinnitus pitch with the frequency of hearing loss. MATERIALS AND METHODS: A total of 500 patients with unilateral or bilateral chronic tinnitus were enrolled in this study. All patients underwent pure tone audiometry (PTA) and tinnitus acoustic examination. Hearing loss levels and frequencies were recorded. The relationship between tinnitus pitch and hearing loss level and frequency was statistically analyzed. RESULTS: Our results showed that 96.6% of the 500 tinnitus patients had hearing loss. Statistical analysis showed that low frequency (LF) tinnitus was correlated with LF hearing loss, but moderate frequency & high frequency (MF&HF) tinnitus was not significantly associated with MF&HF hearing loss. The coincidence of tinnitus pitch with the highest hearing threshold correlated with the degree of hearing loss. CONCLUSION AND SIGNIFICANCE: The vast majority of patients with chronic subjective tinnitus had hearing loss, and the frequency of tinnitus correlated with the degree and frequency of hearing loss but not exactly fall within the frequency range of hearing loss.

MCC950 attenuates plasma cell mastitis in an MDSC-dependent manner.

Plasma cell mastitis (PCM) is a sterile inflammatory condition primarily characterized by periductal inflammation and ductal ectasia. Currently, there is a lack of non-invasive or minimally invasive treatment option other than surgical intervention. The NLRP3 inflammasome has been implicated in the pathogenesis and progression of various inflammatory diseases, however, its involvement in PCM has not yet been reported. In this study, we initially observed the pronounced upregulation of NLRP3 in both human and mouse PCM tissue and elucidated the mechanism underlying the attenuation of PCM through inhibition of NLRP3. We established the PCM murine model and collected samples on day 14, when inflammation reached its peak, for subsequent research purposes. MCC950, an NLRP3 inhibitor, was utilized to effectively ameliorate PCM by significantly reducing plasma cell infiltration in mammary tissue, as well as attenuate the expression of pro-inflammatory cytokines including IL-1ß, TNF-α, IL-2, and IL-6. Mechanistically, we observed that MCC950 augmented the function of myeloid-derived suppressor cells (MDSCs), which in turn inhibited the infiltration of plasma cells. Furthermore, it was noted that depleting MDSCs greatly compromised the therapeutic efficacy of MCC950. Collectively, our findings suggest that the administration of MCC950 has the potential to impede the progression of PCM by augmenting MDSCs both numerically and functionally, ultimately treating PCM effectively. This study provides valuable insights into the utilization of pharmacological agents for PCM treatment.

Efficacy and factors influencing outcomes of customized music therapy combined with a follow-up system in chronic tinnitus patients.

BACKGROUNDS: Tinnitus is a meaningless sound signal perceived by the patients in the absence of auditory stimuli. Due to the complex etiology and unclear mechanism, specific therapies for tinnitus are still in the exploratory stage. In recent years, personalized and customized music therapy has been proposed as an effective method for tinnitus treatment. The aim of this study was to explore the efficacy of customized therapy with a well-designed follow-up system in the treatment of tinnitus through a large sample one arm study and to identify the relevant factors affecting the treatment outcome. METHODS: The study investigated a total of 615 patients with unilateral or bilateral chronic tinnitus who received personalized and customized music therapy for 3 months. A complete follow-up system was designed by the professionals. Questionnaires of Tinnitus Handicap Inventory (THI), Hospital Anxiety and Depression Scale (HADS) and Visual Analogue Scale (VAS) were used to evaluate the therapeutic effects and relevant factors affecting the efficacy of therapy. RESULTS: The results showed a decreasing trend in THI and VAS scores after 3 months of therapy, with statistically significant differences between pre- and post-therapy time points (P < 0.001). All patients were divided into 5 groups according to THI scores, and the mean reduction score in catastrophic, severe, moderate, mild and slight group was 28, 19, 11, 5, 0 respectively. The proportion of tinnitus patients with anxiety was higher than that with depression (70.57% and 40.65%, respectively), and there were statistically significant differences between HADS-A/D scores pre- and post-therapy. Binary logistic regression showed that the baseline of THI, VAS scores, the duration of tinnitus and the state of anxiety prior to therapy were significant influencing factors of therapeutic efficacy. CONCLUSIONS: The magnitude of reduction in THI scores after music therapy depended on the severity of the patients' tinnitus, the higher the initial THI scores, the greater the potential for improvement in tinnitus disorders. Music therapy also reduced the anxiety and depression levels of tinnitus patients. Therefore, personalized and customized music therapy with a comprehensive follow-up system may be an effective treatment option for chronic tinnitus patients.

Comparison of the second-line treatments for patients with small cell lung cancer sensitive to previous platinum-based chemotherapy: A systematic review and Bayesian network analysis.

Objective: It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy. Methods: We systematically screened randomized controlled trials from several online databases. The primary outcome was objective response rate (ORR), and the secondary outcomes were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and hematological complications graded 3 to 5. The efficacy of included treatments was ranked by surface under the cumulative ranking curve (SUCRA) value. Results: We included eleven trials involving 1560 patients in quantitative analysis. Triple chemotherapy containing platinum (TP, combination of cisplatin, etoposide, and irinotecan) was associated with favorable ORR (intravenous topotecan vs TP; odds ratio: 0.13, 95% CI:0.03-0.63; SUCRA, 0.94) and PFS (vs intravenous topotecan; hazard ratio, 0.5; 95% CI: 0.25-0.99; SUCRA, 0.90). Belotecan ranked highest for OS (SUCRA, 0.90), while intravenous topotecan plus Ziv-aflibercept ranked highest for DCR (SUCRA, 0.75). TP was more likely to cause anemia and thrombocytopenia while intravenous topotecan plus Ziv-aflibercept resulted in most neutrocytopenia. Conclusion: TP is the first recommendation for the second-line treatment of sensitive relapsed SCLC. TP achieved priority in ORR and PFS with the most frequent adverse effects in anemia and thrombocytopenia. For patients who cannot tolerate the hematological adverse effects of triple chemotherapy, amrubicin is an optional option. Amrubicin had relatively good ORR and PFS, accompanied by fewer hematological complications. The rechallenge of the platinum doublet is inferior to amrubicin in ORR, DCR, and PFS. Oral topotecan has a similar effect compared with IV topotecan, but oral topotecan was associated with slightly higher safety and less stress in nursing. Belotecan contributed to the best PFS with slightly better safety but was not ideal in other outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358256.

Competitive adsorption of heavy metals in aqueous solution onto biochar derived from anaerobically digested sludge.

Heavy metals often coexist in contaminated wastewater systems and their competitive behavior could affect the adsorption capacity of biochar. Till now, the competitive adsorption of heavy metals by biochar derived from anaerobically digested sludge has never been reported. In this work, biochar from anaerobically digested sludge was synthesized and characterized to explore the competitive behavior of widely co-existed Pb(II) and Cd(II). The mutual effects and inner mechanisms of their adsorption on studied biochar were systematically investigated via single-metal and binary-metals systems. In single-metal system, the biochar exhibited much higher adsorption capacity for Pb(II) compared to that for Cd(II). The maximum adsorption capacities of Pb(II) and Cd(II) based on single-component adsorption isotherm were 0.75 and 0.55 mmoL/g, respectively, which were much higher than those reported biochars from different materials. In binary-metals system, the Cd(II) adsorption on biochar was severely inhibited, while the uptake of Pb(II) was not affected significantly. The results of binary-components adsorption isotherm clearly demonstrated the competitive adsorption between two metals occurred as well as the preference of biochar for Pb(II) compared to Cd(II). FTIR and metal characteristics analysis results revealed that Pb(II) had exactly the same adsorption sites with Cd(II), but Pb(II) has a greater affinity than Cd(II), thereby exhibiting a competitive advantage in the coexisting system.